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Michael Japs - Rapid commercialization using an integrated approach tobioprocess development

Michael is a fifteen year veteran of the industrial biotechnologysector leading development, scale-up, and commercializationof novel processes for the production of chemicals viafermentation. In his current role, he is responsible for leadingconceptual process design, economic analysis, and technicalbusiness development for new product opportunities. Hepreviously formed and led Genomatica’s process engineeringdepartment where he was integral in establishing thecompany’s core bioprocess engineering capabilities. He is aninventor of Genomatica’s renewable 1,4-butandediol (BDO)process which in 2013 received the prestigious KirkpatrickChemical Engineering Achievement Award recognizing ‘themost noteworthy chemical engineering technologycommercialized in the world during the past two years…’. Priorto Genomatica Michael held several R&D and operationspositions at NatureWorks LLC commercializing polylactic acid(PLA). Michael holds a B.S. degree in chemical engineeringfrom the University of Minnesota.

SESSION 17: RENEWABLE FUELS,CHEMICALS, AND BIO-BASED PRODUCTSIV: COMMERCIALIZATION AND ECONOMICS

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Symposium on Biotechnology for

Fuels and Chemicals

Michael JapsApril 30th, 2015

Rapid Commercialization using an IntegratedApproach to Bioprocess Development

Abstract: Rapid Commercialization using an IntegratedApproach to Bioprocess Development

Genomatica has developed a complete, commercial-scalebioprocess for production of 1,4-butanediol (BDO) directlyfrom carbohydrates, which has been producing thousands oftons since 2012. This presentation will discuss the integratedapproach inherent to Genomatica’s biotechnology platformthat made this faster and less expensive than traditionalbioprocess development and scale up. A key differentiator ofthis platform includes an emphasis on modeling and techno-economic analysis from the very start; using this informationto guide decisions on organism, fermentation, anddownstream process design. Combining this integratedapproach with real-world commercial expertise enabledhighly-reliable and predictable scale-up and scale-downresults across multiple orders of magnitude.

BDO commercialization journey and success5 years from concept to commercial production

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BDO Producing Organisms – 2008 Purified BDO – 2009 3,000 Liter Piloting – 2010

Integrated Demo Plant – 2011 Shipping Tons at a Time – 2011 Commercialization – 2012

Commercial-scale production2,500 tons in five weeks, Loudon-TN, produced Q4’12

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First Bio-BDO plantunder construction in Italy by Novamont

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Bottrighe, Italy site under construction

BASF licenses the GENO BDOTM process“exceptionally advanced and reliable” process technology

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• Market leader and fully integrated derivativeproducts producer

• Chose Genomatica process because‘exceptionally advanced and reliable’(Sanjeev Gandhi, Member of BASF Board of Executive Directors)

#1 chemical company

#1 BDO producer

535KT BDO capacity

PRESS RELEASE – November 27, 2013

BASF produces first commercial volumes ofbutanediol from renewable raw material

PRESS RELEASE – March 5, 2015

BASF now offers bio-based PolyTHF

Properties identical to conventional PolyTHF

Extends range of products based on renewable raw materials

Opportunity for customers to test new market segments

Kirkpatrick Awardfirst biotechnology winner of this landmark chemical engineering award

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“the most noteworthy chemicalengineering technology

commercialized in the world inthe past two years”

• Award to one company every 2 years

• 80 years of winners have shapedmajor parts of the chemical industry

advantagedprocess

technology

Integrated bioengineering platformdrives high impact innovation, products, solutions

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Proven & Broad Applicability:• BDO commercialization in under 5 years• expansive IP portfolio (500+)• 20+ basic/intermediate chemicals• sugars (C6/C5) & C1 feedstocks

predictivecomputer models

bioprocessengineering

experimentalbiotechnology

bioengineeringplatform

Platform Attributes:• computer-aided design for biology (since 2000)• enables focused efficient experimentation• integrated bioprocess engineering• results in rapid cost-effective development

bioprocessengineering

predictivecomputer models

experimentalbiotechnology

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Bioprocess engineeringintegrated bioprocess design, scale-up and economics

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Bioprocess engineering: capabilitiesintegrated bioprocess design, scale-up and economics

integratedbioprocessengineering

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Core capability: modeling & analysisquantitative approach guides R&D to reduce capex/opex

• Proprietary economic modelingtools identify leverage points

• Process simulation usingAspenPlus, Excel, more

• Reliable modeling offermentations

• Singular focus on metrics

• Design the entire processbefore the first gene is cloned

DashboardDashboard

ProcesssimulationProcesssimulation

Techno-economic analysisTechno-economic analysis

Techno-economic analysiscore competence that focuses R&D on reducing production costs

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Assess potential of new opportunities Identify high-impact areas for optimization Compare economics of design alternatives Provide metrics for tracking performance

Process ModelProcess Model

Technical Metrics(TRY, OUR, impurities, recovery, wastes, etc.)

Cost Impact$/ton

Definition: Combined (simultaneous) process modeling and economic evaluation

Framework for guiding all R&D decisions!

What is our current advantage or disadvantage?

Where arefeedstockprices headed?

How often are we advantaged or disadvantaged?(past 3 years and next year pricing scenarios)

When is the process advantaged? When by 25%?

Sensitivity analysis

What are the keyelements of thecost stack?

Example: modeling and analysiscompetitive dashboards – using TEA to drive cost advantage

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Biotechnology can be advantaged even at $50 oilshown here: GENO BDO vs. best available petroleum-based, 50KT scale

CM

EC

orn

Pri

ce

N.A. Butane Price

0 – 25%

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Core capability: industrial expertiseunique blend of bioprocess engineering and biotech skills

• 25+ experienced engineers

• Built/operated many plants

• Multiple technology transfers

• Ties everything together:process engineering,modeling, economics, safety,fermentation, filtration,distillation, scale-up / down,operations,…

Make customers successfulMake customers successful

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Core capability: scalable bioprocessingaccelerated commercial process delivery: smaller, cheaper, better, faster

• Full capability process lab

– 50 bioreactors

– Wide range of unit ops forseparations and purification

– 30L piloting suite to generate kgsamples

– Integrated LIMS

• Reliable 100,000-fold scaling

• Quantitative small-scalefermentation design

Flexible fermentation capabilitiesFlexible fermentation capabilities

Iterative experiment designIterative experiment design

Example: scalable bioprocessinghighly predictable scale-up/down

Robust performance at commercial-scale

• Fermentation performance across lab, pilot, and demo scales is highly consistent, enabling rapid lab-to-commercial scale development path

• Average commercial-scale performance over ~50 campaign fermentations equivalent to demonstration-scale performancefor same strain (+/-2%)

• Low variability in performance across ~50 campaign fermentations, indicates process robustness and predictability

Consistent scale-up to commercial

13,000L

DemonstrationScale

CommercialScale

~ 50xscale-up

Campaign Strain

Titer 98%Rate 104%Yield 100%

Average fermentationperformance

( ~50 runs at commercialscale vs. average demo

scale)

0%

20%

40%

60%

80%

100%

120%

0 10 20 30 40 50

Batch No.

Percent average commercial-scale IRR'

0%

20%

40%

60%

80%

100%

120%

0 10 20 30 40 50

Batch No.

Percent average commercial-scaleyield

Top 5 Fermentation RunsFermentation Run

Consistent performance across development scales

0%

30%

60%

90%

120%

2L 30L 13kL

BD

O,g

/L(a

s%

of

2L)

0%

40%

80%

120%

160%

2L 30L 13kL

Rate

,g

/L.h

r(a

s%

of

2L)

0%

30%

60%

90%

120%

2L 30L 13kL

Yie

ld,g

/g(a

s%

of

2L)

The end result: GENO BDOTM processcost competitive; capital efficient; enhanced sustainability attributes

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Cost Competitive TodayRobust Improvement Path

Lower Capital per Ton

Continuous stream of innovationssolving new problems, reducing costs, faster time to market

0%

30%

60%

90%

120%

2L 30L 13kL

Novel Pathways & Feedstocks Downstream Purification

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Reliable scale-up Faster Development

Acknowledgments

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Steve Weiss

Jeff Lievense

Mark Burk

Alex Patist

Thank You!

Questions?

The entire Genomatica BDO team(too many people to list!)

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